Our overall objectives are to continue our studies of the biochemical and structural mechanism of the pathologic effects produced by ethanol, particularly upon the liver, the gastrointestinal tract and the endocrine system. The goals set for the current year include the further study of our experimental model of production of alcoholic cirrhosis in the non-human primate, with particular emphasis on the elucidation of the pathogenesis of early stages of portal hypertension and the study of the transitional stages between alcoholic fatty liver and cirrhosis with an evaluation of the role of acetaldehyde as a mediator of the hepatotoxicity of ethanol. We plan to continue to assess in a variety of population groups to what extent the alteration of plasma alpha amino-n-butyric acid can be used as a biochemical marker of alcoholism. We also plan to pursue the elucidation of the biochemical nature of the microsomal ethanol oxidizing system. We have started the development of more effective blood tests of alcoholic liver damage and we also hope to improve our capacity to distinguish precirrhotic lesions. We will assess the value of a "three-level" screening: 1) detection of heavy drinkers based on biochemical markers, 2) detection of liver injury (with necrosis and inflammation) based on improved serum liver tests, (3) detection of alcoholics prone to develop cirrhosis by screening of liver biopsies for pre-cirrhotic lesions. BIBLIOGRAPHIC REFERENCES: Cederbaum, A.I., Dicker, E., Lieber, C.S. and Rubin, E.: Factors contributing to the adaptive increase in ethanol metabolism due to chronic consumption of ethanol. Alcohlism: Clinical and Experimental Research 1:27-31, 1977. Friedman, H.S. and Lieber, C.S.: Cardiotoxicity of alcohol. Cardiov. Med. 2:111-112, 1977.